EGFR mutant-selective inhibitor BLU-701

An orally bioavailable, mutant-selective, fourth-generation epidermal growth factor receptor (EGFR) inhibitor, with potential antineoplastic activity. Upon oral administration, EGFR mutant-selective inhibitor BLU-701 targets, reversibly binds to and inhibits the activity of the activating/ sensitizing mutations EGFR exon 19 deletion (ex19del) and L858R, and the C797S resistance EGFR mutations, including the resistance double mutants ex19del/C797S and L858R/C797S. This prevents EGFR mutant-mediated signaling. This may both induce cell death and inhibit tumor growth in EGFR mutant-overexpressing tumor cells. EGFR, a receptor tyrosine kinase mutated in many tumors, plays a key role in tumor cell proliferation and tumor vascularization. BLU-701 is able to penetrate the blood-brain-barrier (BBB) and could exert its activity against CNS metastases in EGFR-driven tumors. BLU-701 does not inhibit the activity of wild-type (WT) EGFR.